Treatment outcomes of standardized injectable shorter regimen for multi-drugs resistant tuberculosis in Ethiopia: a retrospective cohort study.

BACKGROUND: The injectable shorter multi-drug resistant tuberculosis (MDR-TB) regimen, has been reported to be less costly and more effective in the treatment of MDR-TB compared to the longer regimen. Ethiopia introduced the injectable shorter regimen (SR) in April 2018 following official recommendation by the World Health Organization (WHO) in 2016. While the WHO recommendation was based on evidence coming from extensive programmatic studies in some Asian and African countries, there is paucity of information on patient outcomes in the Ethiopian context. Thus, we aimed to assess the treatment outcomes and identify factors associated with the outcomes of MDR-TB patients on injectable SR. METHODS: A multi-center facility-based retrospective cohort study was conducted in Ethiopia on 245 MDR-TB patients who were treated between April 2018 and March 2020. Data were collected from patients' medical records and analyzed using SPSS version 25. Descriptive statistics was used to summarize the results while inferential analysis was employed to investigate predictors of treatment outcomes and survival status. RESULTS: A total of 245 patients were included in the study, with 129 (52.7%) of them being female. Median age of the patients was 27 (IQR: 21-33). The overall treatment success rate was 87.8%, with 156 (63.7%) cured and 59 (24.1%) patients who completed treatment. The unfavorable outcomes accounted for 12.2%, with 16 (6.5%) treatment failure, 8 (3.3%) death and 6 (2.4%) lost to follow up. Majority of the unfavorable outcomes occurred during the early phase of therapy, with median time to event of 1.8 months (95% CI: 0.99-2.69). The use of khat (a green leafy shrub abused for its stimulant like effect) and being diagnosed with MDR-TB than rifampicin resistant only, were identified as independent factors associated with unfavorable outcomes. CONCLUSION: The injectable SR for MDR-TB was found to have positive treatment outcomes in the context of programmatic management in Ethiopia.

Informed consent form for platelet rich plasma injections: evidence-based and legally guide for orthopaedic surgeons.

Regarding medico-legal malpractice suits, lawyers and insurers focus on informed consent documentation. Unfortunately, there is no standard protocol for obtaining informed consent for platelet-rich plasma (PRP) injections. The objective of the present study was to create a pre-designed, evidence-based informed consent form specifically for PRP injections. The current evidence on the medico-legal implications of PRP injections was accessed, as well as informed consent in general and specifically informed consent in PRP injections. Additionally, we interviewed orthopaedic surgeons and patients who had undergone PRP injections in the past year using a semi-structured approach. A legally valid and evidence-based informed consent form for PRP injections ensures rights, encouraging open communication and transparency between the patient and surgeon. Moreover, if a lawsuit arose, informed consent would be a critical document in surgeons' defence and would withstand scrutiny from lawyers and the judiciary. An evidence-based informed consent form for PRP injections was elaborated and reviewed by a legal expert to ensure adherence to legal proprieties. The final form of the informed consent for PRP injection was administered for one year and validated at our institution.

The impact of plasma-rich platelet injection to perianal sphincters on incontinence and quality of life in patients with rectal cancer after low anterior or intersphincteric resection: a prospective cohort study.

BACKGROUND: Incontinence is not rare after rectal cancer surgery. Platelet-rich plasma may promote tissue repair and generation but has never been tested for the treatment of anal incontinence. This study evaluated the impact of platelet-rich plasma injection on the severity of incontinence and quality of life after low rectal cancer surgery. METHODS: This is a prospective cohort proof of concept study in a colorectal cancer institution. Patients had undergone low anterior or intersphincteric resection for low rectal cancer and had a Wexner score > 4. Ten milliliters of platelet-rich plasma were injected into the internal and external sphincters under endoanal ultrasound (EAUS) guidance. Primary outcome measure was > 2 point improvement in Wexner score (improved group). The patients were assessed with endo-anal ultrasound examination, manometry, the Wexner Questionnaire and SF-36 Health Surveys, and patients were asked whether they used pads and antidiarrheal medications before and 6 months after PRP injection. RESULTS: Of 20 patients included in the study, 14 (70%) were men, and the average age was 56.8 (SD = 9.5) years. No statistically significant difference was found in Wexner scores before and after PRP injection (p = 0.66). Seven (35%) patients experienced a > 2 point improvement in Wexner score. Rectal manometry demonstrated improved squeezing pressure (p = 0.0096). Furthermore, physical functioning scoring (p = 0.023), role limitation (p = 0.016), emotional well-being (p = 0.0057) and social functioning (p = 0.043) domains on the SF-36 questionnaire improved. One (5%) and three (15%) patients stopped using pads and antidiarrheal medications. CONCLUSION: Platelet-rich plasma injection does not restore Wexner scores, but more than one-third of patients may benefit from this application with an improvement of > 2 points in their scores. Platelet-rich plasma injection may improve squeezing pressure and certain life quality measures for incontinent patients after rectal cancer surgery.

In situ assembly of an injectable cardiac stimulator.

Without intervention, cardiac arrhythmias pose a risk of fatality. However, timely intervention can be challenging in environments where transporting a large, heavy defibrillator is impractical, or emergency surgery to implant cardiac stimulation devices is not feasible. Here, we introduce an injectable cardiac stimulator, a syringe loaded with a nanoparticle solution comprising a conductive polymer and a monomer that, upon injection, forms a conductive structure around the heart for cardiac stimulation. Following treatment, the electrode is cleared from the body, eliminating the need for surgical extraction. The mixture adheres to the beating heart in vivo without disrupting its normal rhythm. The electrofunctionalized injectable cardiac stimulator demonstrates a tissue-compatible Young's modulus of 21 kPa and a high conductivity of 55 S/cm. The injected electrode facilitates electrocardiogram measurements, regulates heartbeat in vivo, and rectifies arrhythmia. Conductive functionality is maintained for five consecutive days, and no toxicity is observed at the organism, organ, or cellular levels.

An injectable self-healing alginate hydrogel with desirable mechanical and degradation properties for enhancing osteochondral regeneration.

Articular cartilage and subchondral bone defects have always been problematic because the osteochondral tissue plays a crucial role in the movement of the body and does not recover spontaneously. Here, an injectable hydrogel composed of oxidized sodium alginate/gelatin/chondroitin sulfate (OSAGC) was designed for the minimally invasive treatment and promotion of osteochondral regeneration. The OSAGC hydrogel had a double network based on dynamic covalent bonds, demonstrating commendable injectability and self-healing properties. Chondroitin sulfate was organically bound to the hydrogel network, retaining its own activity and gradually releasing during the degradation process as well as improving mechanical properties. The compressive strength could be increased up to 3 MPa by regulating the concentration of chondroitin sulphate and the oxidation level, and this mechanical stimulation could help repair injured tissue. The OSAGC hydrogel had a favourable affinity to articular cartilage and was able to release active ingredients in a sustained manner over 3 months. The OSAGC showed no cytotoxic effects. Results from animal studies demonstrated its capacity to regenerate new bone tissue in four weeks and new cartilage tissue in twelve weeks. The OSAGC hydrogel represented a promising approach to simplify bone surgery and repair damaged osteochondral tissue.

Reusable vs Single Use: what Are the Device Trade-Offs in Improving Sustainability.

As autoinjector requirements become increasingly diverse and pharma companies look for quicker routes to market, with lower costs and improved sustainability, there is an increasing trend towards devices with a reusable element. The flexibility in reusable elements can be beneficial for pharma companies with access to these platforms, allowing a relatively rapid transition between different drug combinations. However, it can also lead to devices designed to cover a wide range of requirements which are over designed for their actual more limited end use. The challenge of creating both a cost and sustainability optimised platform device is significantly harder than if developing a single use device with a specific purpose in mind. This paper looks at the range of reusable products on the market, examining some of the assertions around the cost and sustainability benefits of these devices as well as where there are trade-offs relative to current single use format devices.

[Approaches and Challenges in the Clinical Application of On-Body Injector(G-Lasta BodyPod)].

The G-Lasta BodyPod(BodyPod), a newly developed on-body injector that automatically injects pegfilgrastim(Peg-G), has been approved for clinical use in Japan. However, its precise operation is yet to be established. Exploring accumulated literature, we reviewed the efficacy and safety of the Peg-G on-body injector used in other countries and determined its eligibility criteria, operating procedures, and troubleshooting guideline. Overseas, the Peg-G on-body injectors were utilized in relatively young patients, approximately 50 years of age. The incidence of on-body injector failure was low(0.1-4.9%)and comprised injection failure, drug leakage, and dropout. We defined eligible patients as those capable of self-management (handling the BodyPod and understanding troubleshooting). For convenience of patients, the BodyPod was applied to them in the outpatient chemotherapy center by nurses with expertise in the application technique. We categorized BodyPod- related issues as(1)allergic symptoms after application and Peg-G injection,( 2)malfunction or failure before initiating the Peg-G injection, or(3)malfunction or failure after initiating the Peg-G injection. In conclusion, a careful understanding of the handling and malfunction of the BodyPod is essential prior to application in clinical settings, along with patient indications and troubleshooting guidelines appropriate for each hospital.

Provider Factors Likely to Impact Access and Uptake of Long-Acting Injectable Cabotegravir for Transgender Women in the United States: Results of a Qualitative Study.

ABSTRACT: Long-acting injectable cabotegravir (CAB-LA) was US Food and Drug Administration-approved in 2021. However, little is known about providers' CAB-LA knowledge, attitudes, challenges, and prescribing preferences for transgender women patients. Understanding this is critical to developing new pre-exposure prophylaxis (PrEP) interventions tailored to transgender women. We conducted 45-min, in-depth Zoom interviews (IDIs) with United States-based health care providers who prescribe PrEP to transgender women. IDIs focused on providers' CAB-LA knowledge/acceptability, willingness to prescribe CAB-LA to transgender women, potential challenges, and solutions to mitigate challenges. Providers ( N = 17) had a mean age of 43 years, and 35.4% ( n = 6) identified as people of color. Most ( n = 12) had basic knowledge of CAB-LA but wanted additional training. All participants found CAB-LA acceptable and were willing to prescribe. Most ( n = 11) anticipated minimal challenges to implementation. Others ( n = 4) reported potential issues, including logistical/scheduling concerns that impede CAB-LA integration and staffing concerns. Many providers expressed support for self-injection ( n = 13) and injections at "drop-in" clinics ( n = 8) to overcome challenges.

Preferences for Injection Device Settings and the Association with Adherence to Growth Hormone Treatment in Patient with Growth Disorders.

Adherence to recombinant human growth hormone (r-hGH; somatropin, [Saizen®], Merck Healthcare KGaA, Darmstadt, Germany) treatment is important to achieve positive growth and other outcomes in children with growth disorders. Automated injection devices can facilitate the delivery of r-hGH, injections of which are required daily for a number of years. The ability to adjust injection device settings may improve patient comfort and needle anxiety, influencing adoption and acceptance of such devices, thereby improving treatment adherence. Here, we present the results of a retrospective observational study which investigated the association between injection device settings and adherence in the first 3 months of treatment in patients with growth disorders. Patients aged ≥2 and <18.75 years of age at treatment start, with ≥3 months of adherence data from start of treatment with the third generation of the easypod® device (EP3; Merck Healthcare KGaA, Darmstadt, Germany) were selected (N=832). The two most chosen combinations of device settings at treatment start were the default settings for injection speed, depth and time, or a slow injection speed and default depth and time. These combinations also demonstrated the highest adherence rates (94% and 95%, respectively) compared to other device settings (89%). A higher proportion of patients with intermediate/low adherence in the first month of treatment (31%, n=18/59) changed the device settings during treatment compared with those with high adherence (16%, n=128/803) (p=0.005). The ability to adjust injection device settings offers a valuable opportunity for personalizing treatment, improving patient comfort and treatment adherence.

Efficacy of Urethral Sphincter Botulinum Toxin A Injection in Patients with Spinal Cord Injury with Dysuria: A Retrospective Cohort Study.

Spinal cord injury (SCI) often leads to neurogenic lower urinary tract dysfunction, causing dysuria and affecting patients' well-being. This study aimed to evaluate the efficacy of a urethral sphincter botulinum toxin A (BoNT-A) injection in patients with SCI and dysuria. This was a retrospective study including 118 patients with SCI who underwent a urethral BoNT-A injection following a standardized protocol for refractory voiding dysfunction. The protocol involved injecting BoNT-A into the urethral sphincter under cystoscopic guidance. Patient demographics, bladder condition parameters, and treatment outcomes were analyzed. Logistic regression and receiver operating characteristic curve analyses were performed to identify predictors of treatment success. Of the 118 patients, 71 (60.1%) showed satisfactory treatment outcomes after the injection. Post-injection status, bladder management, and injection frequency varied significantly among patients with satisfactory and unsatisfactory treatment outcomes. Age, bladder compliance, intravesical pressure, and bladder contractility were indicators of satisfactory outcomes. The first sensation of bladder filling of ≤263 mL, intravesical pressure of ≤28, and bladder contractility index of ≥14 were highly correlated with satisfactory outcomes. A urethral sphincter BoNT-A injection shows promise in managing dysuria in patients with SCI. Understanding bladder condition parameters and patient demographics helps optimize patient selection for this intervention. Further studies are needed to validate these findings and refine treatment protocols.

New concept in selecting blue dye injection site effect on clinical outcome of early-stage breast cancer patients: a retrospective cohort.

BACKGROUND: Clinico-anatomical review and pilot studies demonstrated that intraparenchymal injection at any site, even those not containing the index lesion, or periareolar injections should provide concordant outcomes to peritumoral injections. METHOD: This was a single-center retrospective cohort at King Chulalongkorn Memorial Hospital. The electronic medical records of patients were characterized into conventional and new injection concept groups. The inclusion criteria were patients who had either a mastectomy or BCS along with SLNB. We excluded patients who underwent ALND, received neoadjuvant therapy, or had non-invasive breast cancer. The primary outcome was the 5-year rate of breast cancer regional recurrence. Additionally, we reported on the re-operation rate, disease-free period, distant disease-free period, mortality rate, and recurrence rates both locoregional and systemic. Recurrences were identified through clinical assessments and imaging. SURGICAL TECHNIQUE: 3 ml of 1%isosulfan blue dye was injected, with the injection site varying according to the specific concept being applied. In cases of SSM and NSM following the new concept, the blue dye was injected at non-periareolar and non-peritumoral sites. After the injection, a 10-minute interval was observed without massaging the injection site. Following this interval, an incision was made to access the SLNs, which were subsequently identified, excised, and sent for either frozen section analysis or permanent section examination. RESULT: There were no significant differences in DFS, DDFS or BCSS between the two groups (p = 0.832, 0.712, 0.157). Although the re-operation rate in the NI group was approximately half that of the CI group, this difference was not statistically significant (p = 0.355). CONCLUSION: Our study suggests that tailoring isosulfan blue dye injection site based on operation type rather than tumor location is safe and effective approach for SLN localization in early-stage breast cancer. However, this study has limitations, including being a single-center study with low recurrence and death cases. Future studies should aim to increase the sample size and follow-up period.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Utilization of local pressure devices in pain management during injections: scoping review.

OBJECTIVE: to map scientific evidence regarding the use of local pressure devices in pain relief during injection procedures in patients. METHODS: scoping review, following the recommendations of the JBI Manual for Evidence Synthesis and PRISMA-ScR, with searches conducted in the PubMed, EMBASE, CINAHL, LILACS, and PsycINFO databases, without temporal restrictions and with a cutoff date of March 2023. RESULTS: a total of 1,514 studies were identified, with 20 articles included in the final sample. The ShotBlocker® device was utilized during subcutaneous and intramuscular injections in children and adults, proving beneficial in reducing pain, anxiety, and fear associated with the procedure. FINAL CONSIDERATIONS: the ShotBlocker® is a low-cost, easy-to-use device that can enhance nursing clinical practice during painful procedures. However, studies involving the Brazilian Pikluc® device are scarce. Further research involving both local pressure devices is recommended.

Analysis and mapping of harm reduction research in the context of injectable drug use: identifying research hotspots, gaps and future directions.

BACKGROUND: Harm reduction is a crucial approach in addressing the multifaceted challenges of injectable drug use. This paper presents an analysis and mapping of the existing literature on harm reduction research in the context of injectable drug use. By reviewing a comprehensive set of scholarly articles, this study identifies research hotspots, knowledge gaps, and future directions in the field. The findings provide valuable insights for researchers, policymakers, and practitioners to guide future research efforts and inform evidence-based harm reduction interventions. METHODS: Data for the study was obtained from the Scopus database, using keywords and phrases related to harm reduction and injectable drug use. Validation methods were employed to verify the accuracy and comprehensiveness of the search strategy. Data analysis involved identifying growth patterns, key contributors, mapping frequent terms, identifying research hotspots, and identifying emerging research directions. RESULTS: A total of 971 articles were found, with a notable increase from 2015 to 2022. The International Journal of Drug Policy (n = 172, 17.7%) and the Harm Reduction Journal (n = 104, 10.7%) were the most prolific journals, and the United States (n = 558, 57.5%) had the highest number of publications. The Johns Hopkins University (n = 80, 8.5%) was the most prolific institution. Mapping of frequent author keywords revealed the main keywords, including harm reduction, HIV, hepatitis C, and opioid overdose. The highly cited articles cover a broad time span and focus on topics like naloxone distribution, HIV and hepatitis C transmission, while recent articles concentrate on emerging issues such as the impact of the COVID-19 pandemic, fentanyl-related concerns, stigma reduction, and needle and syringe programs. Both sets of articles share a common focus on harm reduction strategies, but recent publications highlight current challenges and developments in the field. CONCLUSIONS: This study provides insights into research landscape on harm reduction in injectable drug use. Research is concentrated in high-income countries, emphasizing the need for more research in low- and middle-income countries. Recent publications focus on emerging challenges like COVID-19 and fentanyl. Research gaps highlight the need for studies in diverse populations, social determinants, program evaluation, and implementation strategies to enhance harm reduction interventions.

Self-healing and injectable chitosan/konjac glucomannan hydrogel with pH response for controlled protein release.

Dynamic hydrogels with the features of injection, self-healing, and remodeling at the target site have been developed as smart multifunctional biomaterials for drug delivery. However, most self-healing injectable hydrogels are difficult to control protein release after implantation, owing to the deficiency of pH responsiveness, which reduces the bioavailability of proteins. Herein, we propose a facile strategy to endow pH responsiveness into a dynamic hydrogel with both self-healing and injectable capabilities, by crosslinking biomacromolecular backbones via dual pH sensitive dynamic covalent bond. Particularly, oxidized konjac glucomannan (OKGM) can be crosslinked with poly (aspartic hydrazide) (PAHy) and N-carboxyethyl chitosan (CEC) to form dynamic acylhydrazone bonds and imide bonds, respectively, endowing the hydrogel with pH responsiveness and dynamic behaviors. Specifically, PAHy facilitates the formation of acylhydrazone bonds, improving the mechanical properties and pH sensitivity while reducing the degradation behavior of the hydrogels under physiological conditions. Kinetics indicate that the release of bovine serum albumin follows Fick diffusion under different pH conditions. The pH responsive hydrogel with self-healing injectable capabilities has the potential to be used as a controllable and sustain release carrier for protein drugs.

"All-in-one" self-healing and injectable cationic guar gum hydrogel dressing functionalized by bioactive complexes composed of natural small molecules.

Reducing the risk of wound infection is an urgent issue health priority. Antibacterial polysaccharide-based hydrogels have attracted great attention for infectious wounds, attributed to their safe antimicrobial performance and natural non-toxicity and biodegradability advantages. In this study, the "all-in-one" self-adaptive and injectable cationic guar gum (CG)-based polysaccharide hydrogels (FA-TOB/CG) loaded with bioactive complexes were developed for infectious wound healing. The constructed antioxidant and antibacterial ferulic acid (FA)-tobramycin (TOB) bioactive complexes (FA-TOB) were used as the cross-linking agent and introduced into the CG matrix to construct the FA-TOB/CG hydrogel with a three-dimensional porous structure. The sterilization rates of FA-TOB/CG hydrogel against S. aureus and E. coli reached 98 % and 80 % respectively. In addition, the FA-TOB/CG also exhibits enhanced antioxidant performances (DPPH: > 40 %; ABTS: > 90 %; ·OH: > 50 %). More importantly, FA-TOB/CG hydrogel also showed the ability to sustain the release of FA and TOB. These superiorities of the FA-TOB/CG hydrogel enabled it to provide a moist wound environment and promote wound healing by eliminating bacteria, modulating the local inflammatory response, and accelerating collagen deposition and vascular regeneration. Thus, this study may enlarge a new sight for developing multifunctional dressings by incorporating bioactive complexes into polysaccharide hydrogels for infected wounds.

An injectable hydrogel based on sodium alginate and gelatin treats bacterial keratitis through multimodal antibacterial strategy.

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.

An injectable exosome-loaded hyaluronic acid-polylysine hydrogel for cardiac repair via modulating oxidative stress and the inflammatory microenvironment.

Myocardial infarction (MI) is a serious cardiovascular disease with complex complications and high lethality. Currently, exosome (Exo) therapy has emerged as a promising treatment of ischemic MI due to its antioxidant, anti-inflammatory, and vascular abilities. However, traditional Exo delivery lacks spatiotemporal precision and targeting of microenvironment modulation, making it difficult to localize the lesion site for sustained effects. In this study, an injectable oxidized hyaluronic acid-polylysine (OHA-PL) hydrogel was developed to conveniently load adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) and improve their retention under physiological conditions. The OHA-PL@Exo hydrogel with high spatiotemporal precision is transplanted minimally invasively into the ischemic myocardium to scavenge intracellular and extracellular reactive oxygen species, regulate macrophage polarization, and attenuate inflammation in the early phase of MI. In addition, this synergistic microenvironment modulation can effectively reduce myocardial fibrosis and ventricular remodeling, promote angiogenesis, and restore electrophysiological function in the late stage of MI. Therefore, this hyaluronic acid-polylysine to deliver exosomes has become a promising therapeutic strategy for myocardial repair.

Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement.

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.

Enzymatic Digestion of the Intervertebral Disc Alters Intradiscal Injection and Leakage Mechanics.

Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans) and then injected with fluorescent saline using a through-puncture defect protocol. Pressure-volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections.